Some proteins in human cells that are implicated in cancer also have causal roles in neurodevelopmental disorders, raising the possibility of repurposing targeted cancer therapies to help address neurodevelopmental diseases. But a new analysis, led by WashU Medicine researchers and published in Cell Genomics, shows that the same proteins may be acting in different ways in these two types of diseases, complicating the issue of whether a particular cancer intervention would be helpful or harmful for a neurodevelopmental disorder.
The researchers, led by senior author Tychele Turner, an assistant professor of genetics, used the Google DeepMind tool AlphaFold and their own newly developed computational tools to model the disease-causing changes to proteins in almost 40,000 families with neurodevelopmental disorders and in more than 10,000 sequenced tumors representing five cancer types.
In most cases, they found that the changes in any given protein don't overlap in both types of conditions, showing the importance of analyzing the specifics of protein function in a disease before trying to intervene. For example, if a protein's activity is dialed up in cancer but dialed down in a neurodevelopmental disease, then a treatment that decreases the molecule's activity to address the cancer may do harm in the neurodevelopmental disease by further reducing protein activity that is already too low. This work is important for informing efforts to repurpose treatments across these disease types.
Turner worked with the university's Research Infrastructure Services to bring AlphaFold to campus as a universitywide tool available to all investigators.
